Phase I Clinical Study of Haplo-HSCT Combined With Hypoxic 3D-Cultured Umbilical Cord MSC for the Treatment of SAA

Официальное название

Efficacy and Safety of Sequential Infusion of Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells in Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multicenter, Randomized, Phase 1 Trial

Обзор

Efficacy and Safety of Sequential Infusion of Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells in Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multicenter, Randomized, Phase 1 Trial

Подробное описание

The enrolled patients with an HLA-haploidentical relative for HSCT received the fludarabine (Flu) + cyclophosphamide (Cy) + antithymocyte globulin (ATG) conditioning regimen. For the patients with acute SAA (SAA-I), intravenous administration of 30 mg/(m2 day) of Flu and 500-800 mg/(m2 day) of Cy was performed from days -5 to -2, and 5μg/(kg day) of ATG was administered from days -4 to -1. For the patients with chronic SAA (SAA-II), the same treatment of ATG and Cy was applied as above with the supplement of 0.6 mg/(kg 6 h) of busulfan (BU) from days -8 to -5 prior to transplantation. Donor selection and hematopoietic stem cell mobilization and collection were conducted based on the consensus of The Chinese Society of Hematology regarding indications, conditioning regimens, and donor selection for allogeneic hematopoietic stem cell transplantation. On day 0, HSCs were infused intravenously. Both groups received 5 × 10⁵/kg UC-MSCs at 4 h before HSC infusion. The control group was transfused with conventional 2D-cultured UC-MSCs, whereas the experimental group received 3D hypoxia-preconditioned UC-MSCs. Standard GVHD prophylaxis consisted of mycophenolate mofetil, cyclosporine A, and methotrexate (MTX).

Вмешательства

• Препарат 3D hypoxia-preconditioned UC-MSC group
  5 × 10⁵/kg 3D hypoxia-preconditioned UC-MSCs at 4 h before HSC infusion
• Препарат 2D UC-MSC group
  5 × 10⁵/kg 2D UC-MSCs at 4 h before HSC infusion

Первичные конечные точки

• Adverse events [Срок оценки: The incidence and severity of adverse events (AEs) within the first 150 days after haplo-HSCT]

Вторичные конечные точки (5)

• acute GVHD [Срок оценки: 100days after HSCT]
• chronic GVHD [Срок оценки: 1 years after HSCT]
• Surivial [Срок оценки: 1 year after HSCT]
• Rates of relapse [Срок оценки: UP to 2 years after HSCT]
• The implantation [Срок оценки: Up to 4 weeks after HSCT]

Критерии участия

The inclusion criteria were (1) age 6 to 60 years; (2) diagnosis of SAA or very SAA according to the International Aplastic Anemia Study Group\[21\]; (3) without any severe pulmonary, cardiac, liver, or renal diseases or any active infection; and (4) adequate performance status (Eastern Cooperative Oncology Group score 0-2). Exclusion Criteria：(1)Age 6 years or > 60 years; (2)Failure to meet the IAASG-defined diagnosis of SAA/vSAA, or confirmed (3)Fanconi anemia, congenital aplastic anemia (e.g., dyskeratosis congenita, Diamond-Blackfan anemia); (4)Presence of severe pulmonary, cardiac, hepatic, or renal insufficiency; Uncontrolled active infection; (5)Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 3.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• 28 Fuxing Road, Beijing, China. — Пекин

Идентификаторы

NCT: NCT07299123 · S2021-384-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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